preformulation and stability in biological fluids of the retrocyclin rc-101, a potential anti-hiv topical microbicide预制剂稳定生物体液的retrocyclin rc - 101,一个潜在的抗艾滋病局部杀菌剂.pdfVIP

Sassi et al. AIDS Research and Therapy 2011, 8:27 /content/8/1/27 RESEARCH Open Access Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide 1,2 3 1,4 1,4 5 Alexandra B Sassi , Katherine E Bunge , Brian L Hood , Thomas P Conrads , Alexander M Cole , Phalguni Gupta6 and Lisa C Rohan1,2,3* Abstract Background: RC-101, a cationic peptide retrocyclin analog, has in vitro activity against HIV-1. Peptide drugs are commonly prone to conformational changes, oxidation and hydrolysis when exposed to excipients in a formulation or biological fluids in the body, this can affect product efficacy. We aimed to investigate RC-101 stability under several conditions including the presence of human vaginal fluids (HVF), enabling the efficient design of a safe and effective microbicide product. Stability studies (temperature, pH, and oxidation) were performed by HPLC, Circular Dichroism, and Mass Spectrometry (LC-MS/MS). Additionally, the effect of HVF on formulated RC-101 was evaluated with fluids collected from healthy volunteers, or from subjects with bacterial vaginosis (BV). RC-101 was monitored by LC-MS/MS for up to 72 h. Results: RC-101 was stable at pH 3, 4, and 7, at 25 and 37°C. High concentrations of hydrogen peroxide resulted in less than 10% RC-101 reduction over 24 h. RC-101 was detected 48 h after incubation with normal HVF; however, not following incubation with HVF from BV subjects. Conclusions: Our results emphasize the importance of preformulation evaluations and highlight the impact of HVF on microbicide product stability and efficacy. RC-101 was stable in normal HVF for at least 48 h, indicating that it is a promi